This resubmission focuses on assessing implementation and effectiveness of an evidence-based HIV risk reduction intervention (Eban II) for HIV-serodiscordant, heterosexual African-American couples in two geographic areas (Oakland and Los Angeles, CA) that have a high prevalence of HIV and risk conditions among African Americans. This study builds upon the multi-site, NIMH-funded Eban randomized controlled trial, which resulted in the intended outcomes of increased condom use and reduced incidents of unprotected sexual intercourse among committed, serodiscordant couples. Now that efficacy has been established, it is appropriate to test the effectiveness of the intervention as delivered in community-based organizations (CBOs) that serve African American clients. Because the intervention itself is highly innovative, careful, in-depth attention needs to be paid to barriers and facilitators to implementation and sustainability, especially because the participating agencies have no experience with (but strong interest in) delivering treatment to couples. Our primary implementation aims are: (1) To facilitate implementation of an evidence-based intervention for HIV serodiscordant African American couples; specifically, to employ a theory-guided strategy to partner with the CBOs to expose providers to the intervention, facilitate its adoption and delivery with high fidelity, and sustain its use for nine months following the active implementation phase; and (2) Using mixed quantitative and qualitative methods, to document the implementation process and identify barriers and facilitators to adoption, fidelity, and sustainability. Our primary intervention effectiveness aim is to evaluate the effect of Eban II on behavioral and biological outcomes among 180 couples, specifically incidents of protected sex, proportion of condom use, and incident sexually transmitted infections. We also have a secondary aim to determine the cost-effectiveness of implementation, based on implementation costs and potential cost savings. To achieve these aims, a protocol-based implementation approach will be developed and studied using process evaluation mixed methods with conceptual guidance from the Program Change Model, a model of phased organizational change from exposure to adoption, implementation, and sustainability. The study will produce in-depth information regarding an implementation approach that incorporates multiple strategies and tools for optimal uptake and sustainability of this couples intervention. The effectiveness of Eban II will be assessed using a randomized delayed enrollment (waitlist) control design to evaluate the impact of treatment on outcomes at posttest and 3-month follow-up. This study will produce important information regarding the value of this model and model-guided implementation tools and strategies for use in implementing Eban II and other evidence- based programs in diverse treatment settings. Accordingly, research in HIV prevention, clinical effectiveness trials, and implementation will be informed by the study findings. PUBLIC HEALTH RELEVANCE: The goal of this 5-year study is to study implementation of Eban II, an evidence-based risk reduction intervention for heterosexual, African American HIV serodiscordant couples. We will investigate processes and determinants of implementation in 10 community-based organizations (CBOs) in California, and real-world effectiveness of Eban II as it is delivered to 180 couples. Our goal will promote the availability of couple-based services by enhancing organizational capacity in CBOs, reducing risk-taking practices among serodiscordant couples, and contributing empirically to implementation science.